Contrast agents are useful in diagnostic imaging because they make it possible to determine the location, size and conformation of organs or other structures of the body in the context of their surrounding tissues. Cells which make up the tissues of soft non-bony anatomic segments are comprised primarily of water, even among parts that differ markedly in shape and structure such as the liver, pancreas and intestine.
Diagnostic imaging techniques can detect and map variances in the composition of a target object. These imaging techniques can therefore be used to differentiate between normal tissue and tumors, lesions, or blockages, for example. Small tumors and overlapping tissues, however, are difficult to distinguish. In the diagnosis of disorders of the gastrointestinal (GI) tract, for example, blockage or abnormalities in the conformation of loops of intestine lying one on the other are difficult to identify unless the section of the GI tract is filled with a contrast agent that enables definition of volumes and delineation of boundaries.
In conventional radiographic diagnostic imaging procedure, a beam of X-rays passes through a target object and exposes an underlying photographic film. The developed film then provides an image of the radiodensity pattern of the object. Less radiodense areas produce a greater blackening of the film; more radiodense, bony tissues produce a lighter image. Effective contrast agents for X-ray may be either less radiodense than body tissues or more radiodense. The less radiodense agents include air and other gases; an example of a more radiodense contrast material is a barium sulfate suspension.
Computed tomography (CT) is superior to conventional radiography in its ability to image, with extremely high resolution, a succession of thin sections of an object at specific points, lines or planes along the X, Y, or Z axis of the target object. However, because this procedure is also based on the detection of differences in radiodensity, requirements for contrast agents in CT are essentially identical with those for conventional radiography.
Magnetic resonance imaging (MR) systems for body imaging operate on a different physical principle. Generally, MR relies on the atomic properties (nuclear resonance) of protons in tissues when they are scanned with radio frequency radiation. The protons in the tissue, which resonate at slightly different frequencies, produce a signal that a computer uses to tell one tissue from another. MR provides detailed three-dimensional soft tissue images.
Imaging methods used to obtain information about function related structure include single photon emission computerized tomography (SPECT) and positron emission tomography (PET). SPECT uses a molecule normally found in the body in which one of the atoms is replaced by a radioactive atom. The radioactive molecule, which is chosen for its ability to interact with specific tissues, is called a tracer. The tracer emits photons that can be detected as the tissue is scanned at various angles. A computer reconstructs a 3-dimensional color tracer image. PET uses radioactive biologically active tracers to produce 3-D color images with a greater sensitivity than with SPECT. PET can be used in combination with CT to create a complimentary imaging effect. This imaging technique is called CT-PET.
Diagnostic imaging of the region of the GI tract is particularly difficult because it contains anatomic segments which have higher water content than other parts of the body, and also the anatomic segments are in close proximity or overlay one another. Thus, the success of GI tract imaging is predicated upon adequate intestinal distension with a luminal contrast agent.
One conventional technique for providing distension is administering a methylcellulose-water solution via a fluoroscopically placed nasoduodenal tube. Image sets are collected following rapid filling of the entire small bowel, for example. While the technique provides good image quality, many patients perceive the duodenal intubation as traumatizing, thereby tainting the non-invasive character inherent to imaging.
Other conventional contrast agents include CO2 gas, which is known to have an enhancing effect, particularly in the GI tract. Also, GI imaging has been enhanced with mineral oil. It is also known to use fluorocarbons, including brominated perfluorocarbons, as a contrast enhancement medium in radiological imaging as shown in U.S. Pat. No. 3,975,512 to Long. Other contrast agents used with MR include, for example, barium and clay-based media taken by the patient prior to the diagnostic imaging procedure.
An early proposal suggested that air be directly introduced into the desired location in the intestine via intubation (see, e.g., U.S. Pat. No. 4,074,709) as a means of enhancing the GI tract for imaging. Subsequently, in conjunction with the use of barium and clay-based contrast media, it was proposed that one might expand or distend the part under examination by directly introducing powder, granules or tablets into the medium which would then release carbon dioxide into the intestine. Maintaining the gas in aqueous medium proved to be a problem, however, and often required the use of a pressurized vessel to dissolve the gas in the contrast solution (see, e.g., U.S. Pat. No. 4,215,103).
A problem with the conventional contrast media described above is that they do not enable small lesions, such as shallow ulcers, and flat or surface ulcers, to be accurately detected in an anatomic segment. Another problem with conventional contrast media is that they may cause the patient great discomfort. For example, administering the contrast media via intubation is invasive and possibly dangerous if distension of the anatomic segment is not strictly controlled. Also, conventional contrast media can cause patient side effects, such as diarrhea, which not only cause patient discomfort, but may also interrupt and/or delay a medical or diagnostic procedure. Further, traditional contrast media are generally unpalatable when administered orally. For example, patients often describe fluorocarbon media as having a “slick” mouth-feel. Thus, there is a need or a non-invasive, palatable contrast agent with reduced side-effects to the patient. Further, this contrast agent must sufficiently distend the anatomic segment such that sufficient delineation of the anatomic segment is achieved on the diagnostic image. The image must be sufficient to detect tumors, small lesions, shallow ulcers and flat or surface ulcers.
Accordingly, the present invention is directed to non-invasive, palatable formulations for use in a medical or diagnostic procedure, especially for diagnostic imaging of an anatomic segment such as the GI tract. Additionally, the formulations disclosed herein have reduced patient side-effects compared to conventional contrast media.